The proline dehydrogenase locus must be considered as a positional and functional candidate in schizophrenia. It is located in the chromosomal region of the velocardiofacial syndrome on 22q11 that is suspected to contain genes relevant to schizophrenia, and is involved in the metabolism of neurotransmitters. Positive association between single-nucleotide polymorphisms at the proline dehydrogenase locus and schizophrenia further supported the role of proline dehydrogenase in the development of schizophrenia. In order to replicate these findings, we analyzed three single-nucleotide polymorphisms in a sample comprising 299 schizophrenic patients and 300 controls. In addition, we assessed whether proline dehydrogenase also contributes to bipolar affective disorder, because chromosome 22q11 is also implicated in bipolar affective disorder. We therefore included 300 patients with bipolar affective disorder. This is the first study on a potential involvement of the proline dehydrogenase locus in bipolar affective disorder. Neither single marker nor haplotype analysis revealed an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder.
aInstitute of Human Genetics, University of Bonn, Wilhelmstr. 31, D-53111 Bonn
bInstitute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn
cCentral Institute of Mental Health, Division Genetic Epidemiology in Psychiatry, P.O.B. 122120, D-68072 Mannheim
dDepartment of Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn
eLife & Brain Center, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany
Sponsorships: This study was supported by the National Genomic Network (NGFN) of the German Ministry of Education and Research, the Deutsche Forschungsgemeinschaft (SFB 400 subprojects D1 and D3, Graduiertenkolleg GRK 246, FOR 423 subproject D1), the Alfried Krupp von Bohlen und Halbach-Stiftung, the Fund for Scientific Research Flanders (FWO, grant G.0425.02), the Belgium Interuniversity Attraction Pole (IUAP ‘Molecular Genetics and Cell Biology’), and the National Alliance for Research on Schizophrenia and Depression (NARSAD).
Correspondence and requests for reprints to Rami Abou Jamra, M.D., Institute of Human Genetics, University of Bonn, Wilhelmstr. 31, D-53111 Bonn, Germany
Tel: +49 228 287 2170; fax: +49 228 287 2630;
Received 13 October 2004 Accepted 9 November 2004